Crohn's disease-associated adherent-invasive E. coli are selectively favoured by impaired autophagy to replicate intracellularly

Authors

  • Pierre Lapaquette,

    1. Univ Clermont1, Pathogénie Bactérienne Intestinale, JE2526, USC-INRA 2018, Clermont-Ferrand F-63001, France.
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  • Anne-Lise Glasser,

    1. Univ Clermont1, Pathogénie Bactérienne Intestinale, JE2526, USC-INRA 2018, Clermont-Ferrand F-63001, France.
    2. Institut Universitaire de Technologie en Génie Biologique, Aubière F-63172, France.
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  • Alan Huett,

    1. Gastrointestinal Unit and Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston 02141 USA.
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  • Ramnik J. Xavier,

    1. Gastrointestinal Unit and Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston 02141 USA.
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  • Arlette Darfeuille-Michaud

    Corresponding author
    1. Univ Clermont1, Pathogénie Bactérienne Intestinale, JE2526, USC-INRA 2018, Clermont-Ferrand F-63001, France.
    2. Institut Universitaire de Technologie en Génie Biologique, Aubière F-63172, France.
      *E-mail arlette.darfeuille-michaud@u-clermont1.fr; Tel. (+33) 4 73 17 83 76; Fax (+33) 4 73 17 83 71.
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  • Conflict of interest: The authors have declared that no conflict of interest exists.

  • Authors' contribution: Conceived and designed experiments: PL, ALG, RX, ADM. Performed the experiments: PL, AH. Analysed the data: PL, ALG, AH, RX, ADM. Wrote the paper: PL, ALG, RX, ADM.

  • This paper is dedicated to the memory of Anne-Lise Glasser who sadly passed away on 7th September, 2009.

*E-mail arlette.darfeuille-michaud@u-clermont1.fr; Tel. (+33) 4 73 17 83 76; Fax (+33) 4 73 17 83 71.

Summary

Ileal lesions in Crohn's disease (CD) patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC) able to invade and to replicate within intestinal epithelial cells. Recent genome-wide association studies have highlighted the autophagy pathway as being associated with CD risk. In the present study we investigated whether defects in autophagy enhance replication of commensal and pathogenic Escherichia coli and CD-associated AIEC. We show that functional autophagy limits intracellular AIEC replication and that a subpopulation of the intracellular bacteria is located within LC3-positive autophagosomes. In IRGM and ATG16L1 deficient cells intracellular AIEC LF82 bacteria have enhanced replication. Surprisingly autophagy deficiency did not interfere with the ability of intracellular bacteria to survive and/or replicate for any other E. coli strains tested, including non-pathogenic, environmental, commensal, or pathogenic strains involved in gastro enteritis. Together these findings demonstrate a central role for autophagy restraining Adherent-Invasive E. coli strains associated with ileal CD. AIEC infection in patients with polymorphisms in autophagy genes may have a significant impact on the outcome of intestinal inflammation.

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